2Hydroxyestradiol

2-Hydroxyestradiol, also known as 2-OHE2, is a catechol estrogen and a metabolic product of estradiol formed by hydroxylation at the 2-position of the A-ring. In humans, this reaction is catalyzed by cytochrome P450 enzymes, including members of the CYP1 family such as CYP1A1, CYP1A2, and CYP1B1, generating 2-hydroxyestradiol alongside other hydroxylated estrogens.

Biological activity of 2-hydroxyestradiol is generally distinct from that of estradiol. It typically exhibits reduced affinity for estrogen receptors and weaker estrogenic activity; effects are often context- and tissue-dependent, with some studies suggesting potential antiestrogenic actions in certain models.

Metabolism and detoxification occur primarily through catechol-O-methyltransferase (COMT), which methylates 2-hydroxyestradiol to form 2-methoxyestradiol (2-MeOE2). 2-MeOE2 has been studied for antiangiogenic and antiproliferative properties and is investigated for potential therapeutic applications. Alternatively, 2-hydroxyestradiol can be oxidized to reactive quinone species that participate in redox cycling and, under some conditions, DNA adduct formation; such reactions are generally considered less prominent than those associated with the 4-hydroxyestrogen pathway.

Clinical and research relevance centers on the balance of estrogen metabolism, particularly the relative levels of 2- versus 4-hydroxy metabolites and the activity of COMT, which may influence estrogen signaling and cancer risk in some contexts. While attractive as potential biomarkers, the utility of 2-hydroxyestradiol measurements remains an area of ongoing investigation.

See also: 4-hydroxyestradiol, 2-methoxyestradiol, catechol estrogens, estradiol.